The objectives of this proposal are to study the effects of GVHD, CsA and FK506 on T cell ontogeny and to determine whether this results in aberrant T cell function causing susceptibility to autoimmunity. I. Thymic dysfunction in animals treated with CsA or FK506 as determined by Vbeta usage. The effects of CsA and FK506 on positive and negative thymic selection will be studied. Cells that have escaped selection will be analyzed for their functional capacity including their ability to cause autoimmune disease. II. Thymic dysfunction in GVHD as determined by Vbeta usage. The effects of GVHD on positive and negative selection will be explored. furthermore, we will assess whether cells have escaped selection are functional and whether they confer susceptibility to autoimmune disease. III. Immunological consequences of the treatment of GVHD with CsA and FK506. The consequence of GVHD together with CsA or FK506 treatment will be assessed for their combined effect on thymic ontogeny. IV. Influence of GVHD, CsA or FK506 on TcR-Valpha usage. The effect on TcR-Valpha usage subsequent to GVHD or the treatment with either CsA or FK506 will be studied. Whether the function of these cells are changed under these experimental conditions will be assessed.